title: Metabolic activation of CaMKII by coenzyme A.
abstract: Active metabolism regulates oocyte cell death via calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated phosphorylation of caspase-2, but the link between metabolic activity and CaMKII is poorly understood. Here we identify coenzyme A (CoA) as the key metabolic signal that inhibits Xenopus laevis oocyte apoptosis by directly activating CaMKII. We found that CoA directly binds to the CaMKII regulatory domain in the absence of Ca(2+) to activate CaMKII in a calmodulin-dependent manner. Furthermore, we show that CoA inhibits apoptosis not only in X. laevis oocytes but also in Murine oocytes. These findings uncover a direct mechanism of CaMKII regulation by metabolism and further highlight the importance of metabolism in preserving oocyte viability.
authors.affiliation: Department of Biochemistry, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: McCoy
authors.forename: Rashid
authors.initials: R
authors.lastname: Darbandi
authors.forename: Hoi Chang
authors.initials: HC
authors.lastname: Lee
authors.forename: Kavitha
authors.initials: K
authors.lastname: Bharatham
authors.forename: Tudor
authors.initials: T
authors.lastname: Moldoveanu
authors.forename: Christy R
authors.initials: CR
authors.lastname: Grace
authors.forename: Keela
authors.initials: K
authors.lastname: Dodd
authors.forename: Wenwei
authors.initials: W
authors.lastname: Lin
authors.forename: Si-Ing
authors.initials: SI
authors.lastname: Chen
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Tangallapally
authors.forename: Manabu
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Richard E
authors.initials: RE
authors.lastname: Lee
authors.forename: Anang A
authors.initials: AA
authors.lastname: Shelat
authors.forename: Taosheng
authors.initials: T
authors.lastname: Chen
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harris
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Fissore
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Colbran
authors.forename: Leta K
authors.initials: LK
authors.lastname: Nutt
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D053143:Caspase 2 / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D003065:Coenzyme A / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D011485:Protein Binding; D015398:Signal Transduction; D015533:Transcriptional Activation; D014982:Xenopus laevis / Q000254:growth & development / Q000378:metabolism*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D053143:Caspase 2; D003065:Coenzyme A